In the prior art, when L-lysine is produced by a fermentative method, a microbial strain separated from the natural environment or an artificial mutant strain obtained from such a microbial strain is used in order to improve the productivity. A large number of artificial mutant strains producing L-lysine are known. Most of them are S-2-aminoethylcysteine (AEC) resistant mutant strains, and belong to the genus of Brevibacterium, Corynebacterium, Bacillus, Escherichia or Serratia. Further, various techniques have been disclosed for increasing amino acid production, for example, by employing a transformant using recombinant DNA (U.S. Pat. No. 4,278,765).
For example, bacteria belonging to the genus Serratia are widely used as bacteria producing various amino acids such as L-proline, L-histidine, L-arginine, L-threonine, L-valine and L-isoleucine and have excellent properties as amino acid-producing bacteria in various aspects, as described in "Oyo Bunshi Idengaku (Applied Molecular Genetics)" publihed by Kodansha Scientific, 1986, ISBN4-06-139659-5) and "Aminosan Hakko (Amino Acid Fermentation)" published by Gakkai Shuppan Center, 1986, ISBN4-7622-9454-3). Production of various amino acids by using bactria belonging to the genus Serratia has been reported. According to one report (Japanese Patent Publication No. 51-9393 (1976)) which reported that it became L-lysine-productive, a yield (a value given by dividing a concentration of produced L-lysine HCl salt by an initial concentration of a carbon source) is calculated at 5.4%.
Serratia marcescens, which is a representative strain of bacteria belonging to the genus Seratia, is similar to bacteria belonging to the genus Escherichia in its gene structure and mechanism of gene expression and regulation, and a cloning vector usable for recombination of DNA in bacteria belonging to the genus Eschrichia can be used for the bacteria belonging to the genus Serratia (Japanese Patent Application Laid-Open Nos. 2-27980 (1990) and 5-10076 (1993)).
By the way, the dihydrodipicolinate synthase (DDPS) is an enzyme for dehydrating and condensing aspartosemialdehyde and pyruvic acid to synthesize dihydrodipicolinic acid. This reaction is located at an entrance into a branch to proceed to an L-lysine biosynthesis system in biosynthesis of amino acids of the aspartic acid family. This enzyme is known to be in charge of an important regulatory site of the L-lysine biosynthesis as aspartokinase is in bacteria belonging to the genus Escherichia.
DDPS is encoded by a gene called dapA in E. coli (Escherichia coli). The dapA has been cloned, and its base sequence has been also determined (Richaud, F. et al., J. Bacteriol., 297 (1986)).
On the other hand, aspartokinase (hereinafter sometimes abbreviated as "AK") is an enzyme for catalyzing a reaction to convert aspartic acid into .beta.-phosphoaspartic acid, which serves as a main regulatory enzyme in a biosynthesis system of amino acids of the aspartic acid family. AK of E. coli has three types (AKI, AKII, AKIII), two of which are complex enzymes with homoserine dehydrogenase (hereinafter sometimes abbreviated as "HD"). One of the complex enzymes is AKI-HDI encoded by a thrA gene, and the other is AKII-HDII encoded by a metLM gene. AKI is subjected to concerted suppression by threonine and isoleucine and inhibited by threonine, while AKII is suppressed by methionine.
On the contrary, it is known that only AKIII is a simple function enzyme, which is a product of a gene designated as lysC, and is subjected to suppression and feedback inhibition by L-lysine. The ratio of their intracellular activities is AKI:AKII:AKIII=about 5:1:4.
DDPS and AKIII are subjected to feedback inhibition by L-lysine as described above, and it hinders effective production of L-lysine. It is expected that L-lysine can be efficiently produced by fermentation by using a bacterium belonging to the genus Serratia if a mutant enzyme of DDPS or AKIII, which is not subjected to feedback inhibition by L-lysine, can be obtained. However, there is no preceding literature which describes such a mutant enzyme of DDPS, and although there is one report on a mutant enzyme of AKIII (Boy, E., et al., J. Bacteriol., 112, 84 (1972)), no example has been known which suggests that such a mutant enzyme may improve productivity of L-lysine. In addition, they have not been known with respect to genes of an L-lysine biosynthesis system of bacteria belonging to the genus Serratia.